ABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited. AIMS: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients. METHODS AND RESULTS: The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent's University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed. INTERPRETATION: The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Humans , Female , Male , Neoplasms/drug therapy , Prospective Studies , Immune Checkpoint Inhibitors/adverse effects , Sex Factors , Incidence , Immunotherapy/adverse effects , Immunotherapy/methods , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/diagnosis , Observational Studies as TopicABSTRACT
BACKGROUND: Lung cancer is the most common thoracic malignancy, representing the leading cause of cancer-related deaths worldwide with a 5-year survival rate of <10%. SUMMARY: The emergence of targeted therapy and immunotherapy has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). However, for those who are not eligible for such therapy or currently have no available standard treatment options, new precision treatment approaches are needed. Human trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein that is highly expressed on several epithelial tumours including NSCLC. TROP2 is recognized as a promising molecular target for therapeutic development in various types of TROP2-expressing malignancies. As a result, several TROP2-targeted therapeutics have recently been developed for clinical use, such as anti-TROP2 antibodies and TROP2-targeted antibody-drug conjugates. Key Message: This review explores the literature data on the role of TROP2 in cancer development and the potential use of emerging TROP2 antibody-drug conjugates in NSCLC treatment.
Subject(s)
Antigens, Neoplasm/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Adhesion Molecules/metabolism , Immunoconjugates/therapeutic use , Lung Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized/immunology , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Antigens, Neoplasm/immunology , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Adhesion Molecules/immunology , Humans , Immunoconjugates/pharmacology , Lung Neoplasms/metabolism , Molecular Targeted TherapyABSTRACT
This study aimed to present the neuropsychological assessment of MC, a seven-year-old girl, who was diagnosed with acute viral cerebellitis. The protocol included cognitive tests, stress and mood scales, behavioral observation, and interviews with family and school. In the neuropsychological assessment, difficulties in crystallized skills, especially in language and numerical cognition domains, were observed. The results of the neuropsychological assessment were discussed to detail her neurocognitive profile and verify to what extent her impairment could be attributed to the acute viral cerebellitis.(AU)
O estudo teve como objetivo apresentar a avaliação neuropsicológica de MC, menina de sete anos, diagnosticada com cerebelite viral aguda. Foram utilizados testes cognitivos, escalas de humor e estresse, observação comportamental, além de entrevista familiar e escolar. Na avaliação neuropsicológica, foram observadas dificuldades nas habilidades cristalizadas, em especial nos domínios da linguagem e cognição numérica. Os resultados da avaliação neuropsicológica foram discutidos visando detalhar o seu perfil neurocognitivo e verificar em que medida seus prejuízos poderiam ser atribuídos à cerebelite viral aguda.(AU)
Subject(s)
Humans , Female , Child , Language , Learning , Neuropsychology , Mathematics , Cerebellar DiseasesABSTRACT
This study aimed to present the neuropsychological assessment of MC, a seven-year-old girl, who was diagnosed with acute viral cerebellitis. The protocol included cognitive tests, stress and mood scales, behavioral observation, and interviews with family and school. In the neuropsychological assessment, difficulties in crystallized skills, especially in language and numerical cognition domains, were observed. The results of the neuropsychological assessment were discussed to detail her neurocognitive profile and verify to what extent her impairment could be attributed to the acute viral cerebellitis.
O estudo teve como objetivo apresentar a avaliação neuropsicológica de MC, menina de sete anos, diagnosticada com cerebelite viral aguda. Foram utilizados testes cognitivos, escalas de humor e estresse, observação comportamental, além de entrevista familiar e escolar. Na avaliação neuropsicológica, foram observadas dificuldades nas habilidades cristalizadas, em especial nos domínios da linguagem e cognição numérica. Os resultados da avaliação neuropsicológica foram discutidos visando detalhar o seu perfil neurocognitivo e verificar em que medida seus prejuízos poderiam ser atribuídos à cerebelite viral aguda.
